SOCS3经JAK/STAT信号通路调控气道黏蛋白高分泌

摘要

目的 研究细胞因子信号转导抑制因子3(SOCS3)在炎症情况下经JAK/STAT通路调控气道黏液高分泌.方法 培养人气道16HBE上皮细胞,设置空白对照组、白介素(IL)-6处理组、IL-6和microRNA (miR)-203处理组,Westernblot法分析细胞中磷酸化JAK激酶(p-JAK1/2)、SOCS3、黏蛋白(MUC) 5AC蛋白水平;Real-time法检测各组细胞中SOCS3、STAT3、MUC5AC mRNA表达量;ELISA法检测各组培养上清液中p-JAK1/2、SOCS3、MUC5AC蛋白含量.结果 在IL-6刺激下,IL-6处理组的p-JAK1/2、SOCS3、MUC5AC蛋白量及SOCS3、STAT3 mRNA含量较空白对照组显著升高(P＜0.05),IL-6和miR-203处理组的p-JAK1/2、MUC5AC蛋白量及STAT3 mRNA含量较IL-6处理组显著升高(P＜0.05),但SOCS3 mRNA与IL-6处理组比较差异无统计学意义,SOCS3蛋白含量较IL-6处理组显著降低(P＜0.05).结论 细胞在IL-6刺激后SOCS3呈现高表达,同时经JAK/STAT信号通路负反馈调控MUC5AC.%Objective To investigate the SOCS3 regulates mucus hypersecretion via JAK/STAT signal pathway in inflammatory cells.Methods Culture 16HBE cells and divide into three groups:control group,inter leukin(IL)-6-exposed group;IL-6-exposed and microRNA-203-transfered group.The protein levels of JAK1/2,SOCS3 and MUC5AC were measured by Western blot.The mRNA expressions of SOCS3,STAT3 and MUC5AC were detected by Real-time PCR.The protein levels of p-JAK1/2,SOCS3 and MUC5AC were analyzed by ELISA.Results Compared with the control group,the mRNA expressions of SOCS3,STAT3,MUC5AC and the protein levels of p-JAK1/2,SOCS3,MUC5AC were both significantly increased in IL-6-exposed group (P ＜ 0.05);in the IL-6-exposed and miR-203-transfered group,the protein levels of p-JAK1/2,MUC5AC and the mRNA expressions of STAT3 were both significantly increased (P ＜ 0.05),but the mRNA expressions of SOCS3 was almost as much as that in IL-6-exposed group,the protein levels of SOCS3 was significantly decreased (P ＜ 0.05).Conclusion SOCS3 over-express when cells are stimulated by IL-6,and negative-feedback regulates MUC5AC secretion via JAK/STAT signal pathway.